Study on the Mechanism of Competing Endogenous Network of 'Scutellaria barbata D.Don-Houttuynia cordata- Radix Scutellariae' in the Treatment of NSCLC based on Bioinformatics, Molecular Dynamics and Experimental Verification.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Traditional Chinese medicine, known for its multi-target and multi-pathway characteristics, offers a potential treatment approach for NSCLC. OBJECTIVE: This study aimed to explore the mechanism of the competitive endogenous network of 'Scutellaria barbata D.Don-Houttuynia cordata-Radix Scutellariae' in treating NSCLC through bioinformatics analysis and in vitro experiments. MATERIALS AND METHODS: Various databases and ceRNA networks were utilized to collect and screen components and target genes, molecular docking and molecular dynamics simulations to determine the binding ability of ligand-receptor complexes. In vitro experiments were conducted to validate the effects of active ingredients of 'Scutellaria barbata D.Don-Houttuynia cordata- Radix Scutellariae' on non-small cell lung cancer cell line A549. RESULTS: The key target proteins CCL2, EDN1, MMP9, PPARG, and SPP1 were docked well with their corresponding TCM ligands. Among the ligand-receptor complexes, MMP9-Luteolin and MMP9-Quercetin demonstrated the weaking binding force, while the SPP1-Quercetin complex, associated with NSCLC prognosis, exhibited stable structure formation through hydrogen bond interaction during MD simulation. In vitro experiments confirmed the inhibitory effect of Quercetin on SPP1 expression, as well as the proliferation and migration of A549 cells. CONCLUSION: The findings suggest that 'Scutellaria barbata D.Don-Houttuynia cordata-Radix Scutellariae' may potentially treat lung cancer by suppressing the expression of SPP1. This study provides valuable insights and novel research directions for understanding the mechanism of traditional Chinese medicine in combating lung cancer.

KNTC1 knockdown inhibits proliferation and metastases of liver cancer.

To investigate the mechanism of kinetochore-associated protein 1 (KNTC1) in hepatocellular carcinoma. To query the TCGA database for KNTC1 expression in hepatocellular carcinoma. Detection of protein and mRNA levels of KNTC1 in hepatocellular carcinoma cell lines SK-Hep-1, Huh7, HepG2 and SNU449. Cell proliferation, migration and invasion ability were examined after KNTC1 knockdown in SK-Hep-1 and Huh7. Proteins related to KNTC1 were identified through protein interregulation, and their role in hepatocellular carcinoma was investigated. Our results showed that KNTC1 was significantly upregulated in hepatocellular carcinoma tissues and was associated with poorer prognostic survival. The expression of KNTC1 in hepatocellular carcinoma cell lines SK-Hep-1, Huh7, HepG2 and SNU449 was significantly higher than that in normal hepatocyte line L02. Knockdown of KNTC1 in SK-Hep-1 and Huh7 significantly inhibited cell viability, migration ability and invasion ability. KNTC1 is involved in the regulation of hepatocellular carcinoma through its interaction with cyclin-dependent kinase 1 (CDK1). Knockdown of KNTC1 inhibited CDK1 expression, while CDK1 overexpression was able to rescue the regulation of KNTC1 on the viability, migration and invasive ability of hepatocellular carcinoma cell lines. Knockdown of KNTC1 was found to resulted a cell cycle arrest at the S-phase, potentially through the modulation of CDK1, leading to decreased migration and invasion of hepatocellular carcinoma cells. Moreover, knockdown of KNTC1 in mouse transplanted tumors significantly inhibits tumor growth. Inhibition of high expression of KNTC1 in hepatocellular carcinoma was effective in suppressing the progression of hepatocellular carcinoma cells after knockdown. It may be a potential target for the treatment of hepatocellular carcinoma.

Aberrant expression of miR-153 is associated with the poor prognosis of cervical cancer.

Previous studies have demonstrated that microRNAs (miRNAs) are frequently dysregulated in tumors and are associated with the initiation and progression of various types of cancer. miR-153 has been previously shown to have an anti-tumor effect in the majority of cancer types. However, to date, the expression status and function of miR-153 in cervical cancer (CC) remains unclear. In the present study, the expression of miR-153 in CC tissues and cell lines was examined, revealing that the expression of miR-153 was markedly downregulated in the CC tissues and cell lines investigated, when compared with matched noncancerous tissues and normal cervical epithelial cell line. Furthermore, ectopic expression of miR-153 by miR-153 mimic inhibited cell proliferation; however, transfection with the miR-153 inhibitor promoted the cell proliferation in CC cell lines. Finally, the results showed that the downregulation of miR-153 was associated with poor 5-year over survival in CC patients and it could be regarded as an independent biomarker to predict the prognosis of CC patients. Collectively, these results indicated that miR-153 may function as a tumor suppressor in CC, and it may be a potential novel therapeutic target for CC.

A non-synonymous polymorphism in NBS1 is associated with progression from chronic hepatitis B virus infection to hepatocellular carcinoma in a Chinese population.

PURPOSE: Nijmegen breakage syndrome 1 (NBS1) has a vital role in DNA double-strand break (DSB) repair, functioning as a sensor to identify and repair DNA damage and maintaining genomic stability by participating in the intra-S-phase checkpoint. Polymorphisms of NBS1 have been investigated in multiple cancers with variable results. To our best knowledge, no previous study has focused on the association between NBS1 single-nucleotide polymorphisms (SNPs) and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Five NBS1 SNPs were selected based on their potential functional impact. A hospital-based cohort, comprising 481 patients with HBV-related HCC, 508 patients with chronic hepatitis B virus infection (CHB), and 581 healthy controls, was recruited for genotyping analysis. RESULTS: After quality control, four SNPs were successfully genotyped (rs10464867, rs1063053, rs1805794, and rs709816), none of which were significantly associated with HCC or CHB compared with those of healthy controls. Similarly, the combined HBV-infected group (including the HCC and CHB groups) exhibited no significant associations with these SNPs compared with healthy controls. In contrast, comparison of the frequency of rs1805794 between patients with CHB and those with HCC identified a significant association (P=2.99E-03, odds ratio =1.31, 95% confidence interval =1.10-1.56). CONCLUSION: These findings suggest that, as a non-synonymous SNP, the rs1805794 C/G polymorphism may play a role in the progression from CHB to HCC.

[Molecular mechanism of HL-60 cell apoptosis induced by baicalin].

This study was aimed to investigate the effect of baicalin on proliferation and apoptosis of HL-60 cells and its mechanism. Cell proliferation was assayed by using Cell Counting Kit-8. The morphological changes of HL-60 cells were examined by light microscopy and nucleolus morphological changes were observed by fluorescent microscopy after Hoechst 33342 staining. The early cell apoptosis was detected by using flow cytometry with Annexin V-FITC/PI double staining. The expression of caspase-3, caspase-9, Bcl-2 and Bax mRNA was detected by RT-PCR and Western blot assay was carried out to examine Bax, Bcl-2, caspase-8 and cleaved caspase-3 expression. The results showed that Baicalin inhibited the proliferation of HL-60 cells in a time- and concentration-dependent manner. HL-60 cells exhibited typical morphological features (for example, cell shrinkage, membrane blebbing and formation of apoptotic bodies). Cell apoptosis in early stage could be detected, the expression of caspase-3, caspase-9 and Bax mRNA was obviously up-regulated, while the Bcl-2 expression down-regulated, and accordingly Bcl-2/Bax ratio decreased. Such results were consistent with the expression of these proteins. In addition, the expression of cleaved caspase-8 protein was induced significantly after treated with baicalin. It is concluded that baicalin can significantly inhibit the proliferation of HL-60 cells and induce the apoptosis of HL-60 cells, which may occur through decreasing Bcl-2/Bax ratio by intrinsic pathway and through extrinsic pathway. It suggests that baicalin may be a promising drug for the therapy of acute myeloid leukemia.

The characterization and role of leukemia cell-derived dendritic cells in immunotherapy for leukemic diseases.

Usually, an effective anti-leukemia immune response cannot be initiated effectively in patients with leukemia. This is probably related to immunosuppression due to chemotherapy, down-regulation of major histocompatibility complex (MHC) II molecules, and the lack of co-stimulatory molecules on dendritic cells (DC). In light of this problem, some methods had been used to induce leukemia cells to differentiate into mature DCs, causing them to present leukemia-associated antigens and activating naïve T cells. Furthermore, leukemia-derived DCs could be modified with tumor antigens or tumor-associated antigens to provide a new approach to anti-leukemia therapy. Numerous studies have indicated factors related to the induction and functioning of leukemia-derived DCs and the activation of cytotoxic T-lymphocytes (CTLs). These include the amount of purified DCs, cytokine profiles appropriate for inducing leukemia-derived DCs, effective methods of activating CTLs, reasonable approaches to DC vaccines, and the standardization of their clinical use. Determining these factors could lead to more effective leukemia treatment and benefit both mankind and scientific development. What follows in a review of advances in and practices of inducing leukemia-derived DCs and the feasibility of their clinical use.

Effect of Rta protein of Epstein-Barr virus on the cell cycle in HeLa cells.

Epstein-Barr virus (EBV) replication and transcription activator (Rta) is an immediate-early transcription factor that mediates the switch from latent to lytic infection. DNA viruses often modulate the function of critical cell cycle proteins to maximize the efficiency of virus replication. Here we have examined the effect of Rta on cell cycle progression. Cell cycle analysis revealed that Rta induced HeLa cells in G0/G1-phase to reenter the S-phase. Analysis of the expression pattern of a key set of cell cycle regulators revealed that expression of Rta inhibited the expression of Rb and p53 and induced the expression of E2F1. These findings suggest that Rta plays an active role in redirecting HeLa cell physiology through an Rta-mediated cell cycle transformation.